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US8420397B2 - Fluid flow device and assembly employing a temperature gadient for determining at least one characteristic of a physico-chemical system therewith - Google Patents

Fluid flow device and assembly employing a temperature gadient for determining at least one characteristic of a physico-chemical system therewith Download PDF

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Publication number
US8420397B2
US8420397B2 US12/445,213 US44521307A US8420397B2 US 8420397 B2 US8420397 B2 US 8420397B2 US 44521307 A US44521307 A US 44521307A US 8420397 B2 US8420397 B2 US 8420397B2
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physico
chemical system
chemical
storage
channel
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US20110032513A1 (en
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Mathieu Joanicot
Philippe Laval
Jean-Baptiste Salmon
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Centre National de la Recherche Scientifique CNRS
Rhodia Operations SAS
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Rhodia Operations SAS
Centre National de la Recherche Scientifique CNRS
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G01N35/085—Flow Injection Analysis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/117497—Automated chemical analysis with a continuously flowing sample or carrier stream
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/117497—Automated chemical analysis with a continuously flowing sample or carrier stream
    • Y10T436/118339—Automated chemical analysis with a continuously flowing sample or carrier stream with formation of a segmented stream
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25625—Dilution
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25875—Gaseous sample or with change of physical state

Definitions

  • the present invention relates to a fluid flow device, an assembly for determining at least one characteristic of a physico-chemical system comprising such a device, a determination method employing this assembly, and a corresponding screening method.
  • a physico-chemical system of which it is proposed to determine at least one characteristic, may be a pure substance, but also a compound, such as one or more solute(s) dissolved in a solvent for example, or alternatively a mixture of several pure substances.
  • a characteristic of this physico-chemical system is in particular a characteristic curve of such a system, in particular a thermodynamic limit, especially a phase diagram, such as a solubility curve, or alternatively the miscibility limit for a mix of two liquids.
  • the present invention aims more specifically, but not exclusively, to study the solubility of such a physico-chemical system.
  • solubility of a solute in a solvent is the maximum concentration of this solute that can be dissolved in this solvent at a given temperature.
  • the solubility curve of this solute which therefore forms a physico-chemical system according to the invention, corresponds to the variation of this solubility as a function of temperature.
  • the invention proposes to remedy this shortcoming. It aims in particular to propose a solution enabling reliable determination of at least one characteristic of a physico-chemical system, accompanied by an appreciably reduced handling time in relation to the prior art.
  • a fluid flow device comprising:
  • this device furthermore comprises means ( 4 , 6 , 12 , 18 ) for forming a succession of slugs (G 1 -G 6 ) in a carrier phase (P) in the connecting channel ( 20 ) and each storage channel ( 22 ); particularly when the means for forming slugs comprise at least a first feed channel ( 4 , 6 ) for the component(s) of said slugs, along with a second feed channel ( 12 ) for the carrier phase, forming an intersection with the or each first feed channel; and/or when the cross section of the connecting channel ( 20 ) and of each storage channel ( 22 1 - 22 6 ) is between 100 ⁇ 2 and 25 mm 2 , particularly when the connecting channel and each storage channel are microchannels ( 20 , 22 1 - 22 6 ), the cross section of which is between 100 ⁇ m 2 and 1 mm 2 and/or wherein each valve (V 1 -V 6 ) is of the tube-pinching type.
  • the fluid flow device as defined above can be further characterized in that the opening ( 22 ′ 1 ) of each storage channel ( 22 1 - 22 6 ) is connected with a corresponding valve (V 1 -V 6 ) by means of a connecting member ( 24 , 26 ) independent of the plate ( 2 ), can be further characterized in that the end of each storage channel ( 22 1 - 22 6 ) opposite the connecting channel ( 20 ) is connected with a rigid tube ( 24 ) which opens into a flexible tube ( 26 ) suited to cooperate with a corresponding tube-pinching valve (V 1 -V 6 ); and/or can be further characterized in that the storage channels ( 22 1 - 22 6 ) are parallel to one another; particularly when the parallel storage channels ( 22 1 - 22 6 )are perpendicular to the connecting channel ( 20 ).
  • the fluid flow device as described above can be characterized in that between two and fifteen, preferably between five and ten, storage channels ( 22 1 - 22 6 ) are provided, particularly when the means adapted to apply a gradient comprise a first source ( 32 1 ) placed close to a first end of each storage channel, along with a second source ( 32 2 ) placed close to a second end of each storage channel, the first and second sources being adapted to apply different conditions, in particular different temperatures.
  • the subject of the invention is also an assembly for determining at least one characteristic of a physico-chemical system, comprising a fluid flow device as described above, analysis means ( 34 ) adapted to identify at least two different states of the physico-chemical system, or of a physico-chemical whole comprising said physico-chemical system, in each storage channel, along with processing means ( 36 ) connected to the analysis means ( 34 ).
  • the subject of the invention is also a method for determining at least one characteristic of a physico-chemical system employing a determination assembly as described in the preceding paragraph, in which method:
  • the subject of the invention is finally a screening method for screening several physico-chemical systems, in which several physico-chemical systems are prepared, at least one characteristic of each physico-chemical system is determined as in one of the determination methods defined above, and at least one preferred physico-chemical system having at least one preferred characteristic is identified.
  • FIG. 1 is a front view schematically illustrating a determination assembly according to the invention
  • FIGS. 2A and 2B are side views illustrating two positions of a valve equipping the determination assembly of FIG. 1 ;
  • FIG. 3 is a graph illustrating a solubility curve that the invention proposes to determine
  • FIGS. 4A to 4C are front views, similar to FIG. 1 , illustrating different steps of implementing the determination method according to the invention
  • FIG. 5 is a larger scale view of FIG. 4 ;
  • FIG. 6 is a graph, similar to FIG. 3 , on which a curve obtained according to the invention is plotted.
  • FIG. 1 illustrates a determination assembly according to the invention which comprises first of all a fluid flow device, denoted as a whole by the reference number 1 .
  • This device comprises a plate 2 which is made in a manner known per se, for example made of PDMS (polydimethylsiloxane).
  • PDMS polydimethylsiloxane
  • This plate 2 has a length and a width typically between 5 and 10 cm, and a typical thickness of 5 mm. It is etched with various microchannels according to conventional procedures of the prior art, which are described in particular in “D. C. DUFFY, J. C. McDONALD, Olivier J. A. SCHUELLER, George M. WHITESIDES, ANAL. CHEM., 70, pp. 49744984, 1998”.
  • the characteristic cross sectional area of these microchannels is typically between 100 ⁇ m 2 (for example 10 ⁇ m by 10 ⁇ m) and 1 mm 2 (for example 1 mm by 1 mm). This size typically causes a laminar flow within these microchannels, with a Reynolds number less than 10.
  • Stéphane COLIN may be mentioned, Microfluidique (EGEM microsystems series, published by Hermes Sciences Publications).
  • millifluidic flow channels that is channels whose cross section is greater than the values mentioned above.
  • the cross section of these millifluidic channels may reach a value close to 9 mm 2 , or 3 mm by 3 mm for example, or even close to 25 mm 2 , or 5 mm by 5 mm for example.
  • FIG. 1 illustrates in particular detail the design of the microchannels that are engraved on the plate 2 .
  • Two feed microchannels 4 and 6 are found first of all, feeding two first components, which are associated with two inlets 8 and 10 .
  • Each of the latter is suited to receive a first end of a tube that is not shown, the other end of which is connected to a syringe, also not shown.
  • the flow rate of the component administered by each syringe is controlled by means of a syringe pump, also not shown.
  • a microchannel 12 is provided, associated with an inlet 14 which interacts with a tube, with a syringe, and with a syringe pump, which are not shown.
  • This microchannel 12 is divided into two branches 16 making roughly the shape of a square, which meet again at an intersection 18 .
  • a mixing microchannel 19 into which the downstream ends of the two microchannels 4 and 6 open, interacts with this intersection 18 .
  • a channel called the connecting channel 20 extends longitudinally, in this case vertically.
  • This connecting channel 20 is provided with an outlet 20 ′, which, it should be noted, is optional. It is caused to interact with several channels called storage channels 22 1 to 22 6 .
  • the term “several” means “at least two”.
  • these storage microchannels extend horizontally, that is to say that they are parallel to each other while being perpendicular to the connecting channel 20 .
  • the connecting channel 20 and the various storage channels 22 1 to 22 6 define a comb, the base of which is formed by the connecting channel and the teeth of which are formed by the storage channels.
  • the various storage channels thus extend in parallel from this connecting channel.
  • this connecting channel and these storage channels define a quadrilateral, one side of which is formed by the connecting channel 20 , two additional sides of which are defined by the end storage channels 22 1 and 22 6 , and a last side of which is defined by a segment parallel to the connecting channel 20 which links the downstream outlets of the various storage channels.
  • the aforementioned quadrilateral is a rectangle.
  • the storage microchannels 22 1 to 22 6 are represented as six in number. However, in practice a number of these channels is used that is advantageously between two and fifteen, preferably between five and ten. It is also possible to envisage using a single storage microchannel.
  • valves V 1 to V 6 At their downstream end, situated on the right of FIG. 1 , the storage microchannels interact with valves V 1 to V 6 , illustrated schematically, one V 1 of which is shown in greater detail in FIGS. 2A and 2B .
  • the opening 22 ′ 1 of the microchannel 22 1 is connected with a rigid tube 24 , made for example of fluorinated ethylene propylene (Teflon® FEP) or polyetheretherketone (PEEK®), that is to say that it does not radially deform appreciably when a liquid is flowing.
  • This rigid tube 24 then opens into a flexible tube 26 , made of PVC or silicone for example, which is associated with the valve V 1 .
  • the latter is a tubepinching solenoid valve, of a type known per se.
  • the tubes 24 and 26 form a connecting member, linking the opening 22 ′ 1 of the microchannel 22 1 with the valve V.
  • This connecting member is independent of the plate, that is to say it may be fitted, especially in a removable manner, to the walls of the aforementioned opening. This is advantageous to the extent that it is possible to make the plate 2 of any material, independently of the nature of the valve and its connecting member.
  • This solenoid valve V 1 is provided in a conventional manner with a piston 28 suited to being actuated by a coil (not shown), capable of squashing the tube 26 against a support 30 .
  • a coil not shown
  • the length l of the flexible tube 26 between its connection with the rigid tube 24 and the area pinched by the piston 28 , is very small, for example close to 2 mm. This makes it possible to limit parasitic movements of the fluid in the various channels when the valve is being operated.
  • valve shown in FIGS. 2A and 2B is advantageous. This is because this valve is physically isolated, due to the presence of the flexible tube 26 , in relation to the fluid present in the storage microchannels. Furthermore, this valve is reliable while having a cost price that is relatively low.
  • the invention foresees applying two gradients along the two dimensions x and y, respectively defined by the storage microchannels 22 and the connecting microchannel 20 .
  • an operating condition gradient is applied, especially of temperature, humidity, illumination, or alternatively of the concentration of another compound.
  • the determination assembly comprises means making it possible to apply such a gradient along the channels 22 .
  • these means comprise two Peltier effect modules 32 1 and 32 2 making it possible to apply a temperature gradient.
  • a Peltier effect module is able to cause temperature variations as a function of an electric current that is applied to it.
  • the first 32 1 of these modules is located close to the upstream end of the storage microchannels 22 , illustrated on the left of FIG. 1 . Furthermore, the second 32 2 of these modules is provided close to the downstream end of these same channels, namely that located on the right of this figure, where these two modules are shown in dot-and-dash lines. As will be seen in greater detail in what follows, each of these modules 32 1 and 32 2 is capable of constituting a hot source or a cold source, depending on the steps of the method according to the invention.
  • the determination assembly is provided with means suitable for analyzing the content of the various microchannels formed in the plate 2 .
  • visual analysis means are involved, namely a microscope 34 represented schematically, the beam of which is directed towards the various storage microchannels 22 .
  • the microscope 34 which is associated with viewing apparatus (not shown), is connected in a conventional manner to a processing computer 36 .
  • solubility curve of a solute in a solvent such as that shown in FIG. 3 .
  • the ycoordinates correspond to the solute concentration C in the solvent, while the temperature T is plotted on the xaxis.
  • the solute is entirely liquid, while above and to the left of this same curve crystals of the solute may form in the solution.
  • this solute A constitutes a physico-chemical system that the invention proposes to study, which may be introduced into the microchannel 4 .
  • the aforementioned solvent B may be admitted through the microchannel 6 , so that the mixture of the solute and the solvent forms a physico-chemical whole in the sense of the invention.
  • a carrier phase P such as oil, which is immiscible with the mixture of the solute and the solvent, is admitted through the microchannel 12 .
  • the various microchannels 20 and 22 are filled, along with the tubes 24 and 26 , by means of oil or alternatively any suitable liquid, which makes it possible to eliminate problems due to the compressibility of air.
  • the various valves V 1 to V 6 are moreover closed.
  • the first valve V 1 alone is opened ( FIG. 4A ), while admitting the solute A and the solvent B through the microchannels 4 and 6 , and oil through the microchannel 12 .
  • a succession of drops G 1 is formed in a manner known per se, which drops are directed towards the first storage channel 22 1 .
  • Each drop is formed by the mixture of the solute A and of the solvent B, that is to say the physico-chemical whole defined above.
  • These drops G 1 are separated from each other in a conventional way by sections of oils, forming a carrier phase P that is immiscible with these drops. It will be noted that, during this step, a sufficiently high temperature is applied for the solute to be completely in liquid form within the drops G 1 , that is to say below and to the right of the curve CS of FIG. 3 .
  • the values of the respective flow rates of solute and solvent admitted by the channels 4 and 6 make it possible to know the concentration C 1 of solute in the various drops G 1 .
  • the sum of flow rates of the solute and of the solvent is between 0.1 mL/hr and 5 mL/hr, especially between 0.5 and 1 mL/hr.
  • the flow rate of oil, admitted through the microchannel 12 is between 0.5 and 10 mL/hr, especially between 1 and 5 mL/hr.
  • the first valve V 1 is closed, according to the procedure made explicit in FIG. 2B , while opening the second valve V 2 ( FIG. 4B ), according to the procedure of FIG. 2A . Furthermore, the respective flow rates of solute and of solvent are modified so as to form drops G 2 in which the solute concentration C 2 is different to that C 1 previously mentioned.
  • FIG. 4B illustrates.
  • the various microchannels 22 1 to 22 6 are iteratively filled by means of different drops G 1 to G 6 for which the solute variations vary from C 1 to C 6 .
  • this concentration varies along the y-axis in the various microchannels 22 .
  • This concentration may thus vary in a determinable manner with the ycoordinates of the microchannels, especially in a monotonic manner, for example linearly, exponentially or alternatively logarithmically.
  • the filling of the various microchannels 22 has been carried out at high temperature so that the various drops G 1 to G 6 are in an entirely liquid state.
  • the prevailing temperature in these microchannels 22 is then lowered so as to move towards the part situated above and to the left of the curve C of FIG. 3 , and so as to crystallize the solute present in the whole of these drops.
  • This temperature change is obtained by suitably changing the electric current supplied to the Peltier modules 32 1 and 32 2 .
  • a temperature gradient is applied along the various storage channels 22 1 to 22 6 .
  • the Peltier module on the left 32 1 is controlled so as to generate a relatively low temperature at its surface, close for example to 10° C.
  • the module on the right 32 2 is controlled so as to generate a relatively high temperature, for example of around 60° C.
  • the application of these different temperatures leads to an approximately linear gradient along each microchannel 22 .
  • the temperature is close to that applied by the module 32 1 while at the downstream end the temperature is close to that applied by the module 32 2 .
  • An analysis step is then proceeded to so as to identify the drops of the storage microchannels 22 where crystals are present.
  • This analysis is carried out visually by means of a microscope 34 .
  • this microscope 34 has a large field of vision so as to observe the whole of the plate at the same time. It is, for example, a binocular microscope.
  • G i ′ denotes the drops in which crystals are present and G i ′′ the drops lacking them.
  • the drops having crystals are situated on the left, that is to say on the side of the lowest temperature.
  • G i ′ ( 1 ) and G i ′′( 1 ) denote the two adjacent drops having different states, one of which is crystallized and the other not crystallized.
  • the drop G i ′( 1 ) is the drop having the highest temperature among all those crystallized
  • the drop G i ′′( 1 ) is the drop having the lowest temperature among all those not crystallized. From this two temperatures, denoted T i ′ and T i ′′ respectively, which correspond to the drops thus identified, are then deduced.
  • T i ( T i ′+T i ′′)/2.
  • the computer 36 locates the various values T 1 to T 6 thus obtained for the concentrations C 1 to C 6 on the graph of FIG. 6 . From these various points a solubility curve CS′ is therefore obtained, shown in FIG. 6 , which is close to that CS of FIG. 3 .
  • the solubility curve has been traced starting with six points, corresponding to six storage microchannels. It will be understood that if it is wished to improve the precision of the method of the invention, this involves increasing the number of storage microchannels, which makes it possible to increase correspondingly the number of points from which the solubility curve is produced. It is also possible to increase the number of drops present in one and the same storage channel, which contributes to reducing the distance between two adjacent drops. This makes it possible to improve the precision on the solubility temperature.
  • the invention is not limited to the example described and shown.
  • the concentration of the solute varies along the yaxis, that is to say for the different channels.
  • the storage channels are filled by means of a physico-chemical whole for which the solute concentration is constant but the proportion of the two aforementioned solvents is variable.
  • the concentration of impurities in the drops tends to vary.
  • the temperature has been varied along the various storage channels, that is to say along the xaxis.
  • a different operating condition such as the relative humidity, the illumination or the variation in concentration of another compound.
  • the analysis is visual in type, due to the use of the microscope 34 .
  • drops having two different states namely a crystallized state and a noncrystallized state
  • these different states identified according to the invention, may be of a different type, namely for example a simple liquid on the one hand, and the presence of two immiscible liquids on the other hand. It is thus possible to obtain a characteristic curve different from a solubility curve, namely the miscibility limit in the case of liquidliquid equilibria.
  • the invention makes it possible to attain the previously mentioned objectives.
  • the operations of filling the various storage channels, carried out according to the invention prove to be clearly faster than the successive operations that must be proceeded with in the prior art. Furthermore, it is possible, thanks to the invention, to carry out a direct reading of the characteristic sought, in particular by means of a simple visual analysis.
  • drops of particularly small volume are advantageous. This is because these drops are true microreactors which, given their scale, are homogeneous and therefore do not require agitation, as might be the case for macroscopic systems. This drop size also ensures rapid attainment of thermal equilibrium.
  • the use of slugs is advantageous in terms of the precision of the determination of the characteristic sought.
  • the various slugs present in the storage channels constitute individual entities, capable of thus preserving their original properties, in particular their initial concentration.

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PCT/FR2007/001667 WO2008046989A1 (fr) 2006-10-13 2007-10-12 Dispositif d'écoulement fluidique, ensemble de détermination d'au moins une caractéristique d'un système physico-chimique comprenant un tel dispositif, procédé de détermination et procédé de criblage correspondants

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US20230128269A1 (en) * 2021-10-22 2023-04-27 Enplas Corporation Fluid handling device and fluid handling system including the same

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US20160341754A1 (en) * 2014-01-31 2016-11-24 CARNEGIE MELLON UNIVERSITY, a Pennsylvania Non-Pro fit Corporation Device and Method for Clinical Data Sampling and Specimen Banking
US10060939B2 (en) * 2014-01-31 2018-08-28 Carnegie Mellon University Device and method for clinical data sampling and specimen banking
US20230128269A1 (en) * 2021-10-22 2023-04-27 Enplas Corporation Fluid handling device and fluid handling system including the same

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FR2907228B1 (fr) 2009-07-24
JP2010506185A (ja) 2010-02-25

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